Overexpression of Tyro3 and its implications on hepatocellular carcinoma progression

  • Authors:
    • Yan Duan
    • Winnie Wong
    • Sonja Courtney Chua
    • Hwee Lin Wee
    • Seng Gee Lim
    • Boon Tin Chua
    • Han Kiat Ho
  • View Affiliations

  • Published online on: November 13, 2015     https://doi.org/10.3892/ijo.2015.3244
  • Pages: 358-366
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Abstract

While various tyrosine kinases have been associated with the pathogenesis of hepatocellular carcinoma (HCC), the identification of a dominant therapeutic target among them remains a challenge. Here, we investigated the role of Tyro3, a relatively uncharacterized member of the TAM (Tyro3, Axl and Mer) receptor family. The present study aimed to profile and identify potential association between Tyro3 expression in HCC and cancer phenotypes. RNAs obtained from 55 HCC patients were quantified for Tyro3 expression in both cancerous tissue and the adjacent normal tissue. Expression profile was correlated with clinical data. These observations were further substantiated with in vitro HCC cell culture investigations.Tyro3 was strongly upregulated (>2-fold elevation) in the tumor tissue of ~42% of the patients. It was shown that higher expression level of Tyro3 was associated with the key tumor marker AFP, and the tumor diameter and liver injury marker ALT. Subsequent cell culture models indicated high expression in various HCC cell lines, in particular Hep3B. Gene silencing of Tyro3 in Hep3B effectively reduced cell proliferation, ERK phosphorylation and cyclin D1 expression, indicating a key in maintaining the proliferative state of these cells. Notably, silencing also suppressed the transcriptional and translational expression of HCC tumor marker AFP. Overall, these data suggest that Tyro3 contributes significantly to tumor growth, aggressiveness and liver dysfunction. Inhibition of Tyro3 and its aberrant signaling in tumors with high expression could present new opportunities for HCC treatment.
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January-2016
Volume 48 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Duan Y, Wong W, Chua SC, Wee HL, Lim SG, Chua BT and Ho HK: Overexpression of Tyro3 and its implications on hepatocellular carcinoma progression. Int J Oncol 48: 358-366, 2016
APA
Duan, Y., Wong, W., Chua, S.C., Wee, H.L., Lim, S.G., Chua, B.T., & Ho, H.K. (2016). Overexpression of Tyro3 and its implications on hepatocellular carcinoma progression. International Journal of Oncology, 48, 358-366. https://doi.org/10.3892/ijo.2015.3244
MLA
Duan, Y., Wong, W., Chua, S. C., Wee, H. L., Lim, S. G., Chua, B. T., Ho, H. K."Overexpression of Tyro3 and its implications on hepatocellular carcinoma progression". International Journal of Oncology 48.1 (2016): 358-366.
Chicago
Duan, Y., Wong, W., Chua, S. C., Wee, H. L., Lim, S. G., Chua, B. T., Ho, H. K."Overexpression of Tyro3 and its implications on hepatocellular carcinoma progression". International Journal of Oncology 48, no. 1 (2016): 358-366. https://doi.org/10.3892/ijo.2015.3244